Donor Lymphocyte Infusion (DLI) post allogeneic stem cell transplant (allo-SCT) in Acute Myeloid Leukemia (AML) and High-Grade Myelodysplastic Syndrome (MDS). A longitudinal retrospective study using peripheral blood (PB) CD34+ and CD3+ donor chimerism (DC) monitoring

Tishya Indran; Tongted Das; Jenny Muirhead; Maureen O'Brien; Michael I Swain; Bianca Cirone; Jaqueline Widjaja; Sushrut Patil; David J Curtis

doi:10.1016/j.leukres.2024.107504

Donor Lymphocyte Infusion (DLI) post allogeneic stem cell transplant (allo-SCT) in Acute Myeloid Leukemia (AML) and High-Grade Myelodysplastic Syndrome (MDS). A longitudinal retrospective study using peripheral blood (PB) CD34⁺ and CD3⁺ donor chimerism (DC) monitoring

Leuk Res. 2024 Apr 24:142:107504. doi: 10.1016/j.leukres.2024.107504. Online ahead of print.

Authors

Tishya Indran¹, Tongted Das², Jenny Muirhead³, Maureen O'Brien³, Michael I Swain³, Bianca Cirone³, Jaqueline Widjaja³, Sushrut Patil⁴, David J Curtis⁵

Affiliations

¹ The Malignant Haematology, Transplantation and Cellular Therapy Services, Alfred Health, Melbourne, VIC, Australia; The Walter and Eliza Hall Institute, University of Melbourne, VIC, Australia. Electronic address: indran.t@wehi.edu.au.
² The Malignant Haematology, Transplantation and Cellular Therapy Services, Alfred Health, Melbourne, VIC, Australia; Bio21 Institute, University of Melbourne, VIC, Australia.
³ The Malignant Haematology, Transplantation and Cellular Therapy Services, Alfred Health, Melbourne, VIC, Australia.
⁴ The Malignant Haematology, Transplantation and Cellular Therapy Services, Alfred Health, Melbourne, VIC, Australia; Monash University, Melbourne, VIC, Australia.
⁵ The Malignant Haematology, Transplantation and Cellular Therapy Services, Alfred Health, Melbourne, VIC, Australia; Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia.

PMID: 38703634
DOI: 10.1016/j.leukres.2024.107504

Abstract

Introduction: This longitudinal study was based on the outcomes of Donor Lymphocyte Infusion (DLI) for falling peripheral blood (PB) CD34⁺ and CD3⁺ donor chimerism (DC).

Methods: From 2012 to 2018, data was collected from the BMT database and electronic medical records (EMR). The primary objective was to compare the indication for DLI based on falling PB CD34⁺ or CD3⁺ DC in patients post allo-SCT for AML and MDS and their overall survival (OS).

Results: 18/70 patients met the inclusion criteria. Indications for DLI were i) falling PB CD34⁺ DC ≤ 80 % with morphological relapse, ii) falling PB CD34⁺ DC ≤ 80 % without morphological relapse and iii) falling PB CD3⁺ DC ≤ 80 % without falling PB CD34⁺ DC. Log rank analysis showed falling PB CD34⁺ DC and morphological relapse had significantly lower OS. Linear regression demonstrated better OS post DLI if there was PB CD34⁺ and CD3⁺ chimerism response at 30 days (p = 0.029), GVHD (p = 0.032) and tapering immunosuppression at the time of falling DC (p = 0.042).

Conclusion: DLI for PB CD34⁺ DC values ≤ 80 % and morphological relapse had the lowest OS. In this study, full DC was achieved after DLI even with a PB CD3⁺DC value as low as 13 %, provided the PB CD34⁺ DC remained > 80 %. Further research is vital in CD34⁺ DC as a biomarker for disease relapse and loss of engraftment.

Keywords: Acute Myeloid Leukemia; Allogeneic stem cell transplant; Donor Lymphocyte Infusion; Myelodysplastic Syndrome; Overall survival; Peripheral blood donor CD34(+) and CD3(+) chimerism.